Medulloblastoma is the most common pediatric brain tumor. While up to 80% of patients are cured, there is a subgroup of patients for whom the current aggressive therapies do not work. These patients have tumors which make large amounts of a protein called MYC. This is a very strong driver of cancer cell growth, but MYC is very hard to target directly.
Project Goal
Principal Investigator Name:
Eric Raabe, MD/PhD & Dr. Barbara Slusher, PhD
Project Title:
Pre-clinical Testing of Novel Glutamine Metabolic Inhibitors in MYC-driven Medulloblastoma
More children die from acute lymphoblastic leukemia (ALL) than from any other cancer. NOTCH1 was found to be the most frequent cancer-causing gene in T-ALL. However, in clinical trials anti-NOTCH drugs had too much toxicity and even promoted cancers. The reason for these side effects is that Notch is an important protein that keeps normal tissues healthy. How can we knock out Notch in cancer, but preserve Notch in normal cells? We believe that the answer may be two proteins called Zmiz1 and Ets1.
Principal Investigator Name:
Mark Yat-Fung Chiang, MD/PhD
Project Title:
Selective Epigenetic Regulation of Notch1 in T-cell Acute Lymphoblastic Leukemia
Cell metabolism is a key aspect of cell biology. Tumors frequently have significant alterations in the specific types of nutrients they require and the way in which they use these nutrients. Certain genes are often associated with driving these critical changes in tumor cell metabolism, which in turn define their aggressive nature. In particular, MYCN, a potent gene that is altered in several pediatric cancers, such as neuroblastoma, is capable of driving defined changes in tumor metabolism.
Project Goal
Principal Investigator Name:
Eveline Barbiere, MD
Project Title:
Targeting MYCN-amplified Neuroblastoma Through RORalpha Activation
Cancer takes the lives of more children than any other disease and leukemia is the most common type of childhood cancer. African-American children with leukemia die more often than children of other races with leukemia. The reasons for this difference between African-American and Caucasian children are unknown. While there are many possible causes of this difference, we have found in previous research that African-American children come to the hospital sicker than Caucasian children prior to the start of chemotherapy.
Principal Investigator Name:
Lena Winestone, MD
Project Title:
Investigating Racial Disparities in Pediatric Acute Leukemia
Sarcomas are tumors of the bone and soft tissues that comprise up to 20% of cancer diagnoses in children. Despite dismal outcomes for patients with recurrent or metastatic disease, treatment regimens consisting of intense non-specific chemotherapy combined with surgery or radiation remain largely unchanged for decades.
Principal Investigator Name:
Asmin Tulpule, MD/PhD
Project Title:
A CRISPRi Genetic Screen in Ewing sarcoma Identifies a Novel Dependence on Homologous Recombination DNA Repair
Ewing’s sarcoma is an aggressive pediatric bone tumor characterized by the EWS/FLI fusion gene. While advances in multimodal therapy have raised disease-free survival rates above 70% for patients with localized disease, survival rates for in metastatic and refractory cases remain stuck below 30%. We need better therapeutic strategies for these patients. EWS/FLI remains challenging to treat with drugs directly and sequencing of patient tumors failed to identify additional drug-treatable mutations common across patients.
Principal Investigator Name:
Emily Theisen, PhD
Project Title:
Bad Influence: EWS/FLI Alters LSD1 and NuRD Interactions to Enforce Oncogenic Function in Ewing’s
Emma is a beautiful little girl born with an unfortunate complication: Beckwith-Wiedemann Syndrome. This rare genetic disorder comes with a statistically higher risk of developing cancer. Emma is screened regularly, getting the best care she can.
